Rotaviruses are the single most important cause of severe diarrhea in infants and young children in both developed and developing countries, accounting for 30-50% of such illnesses. The "Jennerian" approach to vaccination, which involves the use of an attenuated, antigenically- related live virus strain derived from a non-human host, has been evaluated in clinical trials using surrogate rotavirus strains of bovine origin by others or of rhesus monkey origin by us. This approach has had limited success because serotype-specific immunity against each of the four clinically important human rotavirus VP7 serotypes could not be achieved consistently in infants less than six months of age with such an orally administered monovalent vaccine. We, therefore, developed a modified "Jennerian" approach that involved formulation of a quadrivalent rotavirus vaccine containing: (i) rhesus rotavirus (RRV) (VP7 serotype 3), and (ii) three human rotavirus-RRV reassortants, each possessing ten RRV genes and a single human rotavirus gene that encodes VP7 serotype 1, 2, or 4 specificity. Placebo-controlled field trials of individual reassortant vaccines or the quadrivalent vaccine involving 8600 infants and young children in the United States or overseas have been completed, are in progress or are under analysis. The modified strategy developed in LID appears to be quite promising, especially with regard to preventing the the most serious consequences of rotavirus infection, namely severe diarrhea. A significant reduction in the incidence of rotavirus diarrhea of any severity was observed in the two most, recent large clinical trials in the US. Protective efficacy was 63% and 49%, respectively (Sack et al. and Dennehy et al., Abstracts). Of particular significance was the observation that the quadrivalent LID vaccine was even more effective against severe rotavirus diarrhea, as 80% protective efficacy was achieved in the second study.